The geography of the city dictated that the intersection would become prominent, even before the area became built-up. The confluence of Portage Avenue (originally known as Queen Street) and Main Street lies just a few hundred metres from The Forks, the confluence of the Red River of the North and Assiniboine River. The area had long been a gathering and trading site for aboriginal Canadians, and within a few years of white settlement in the region, dirt trails paralleled the paths of the rivers. These trails roughly where Portage and Main meet today.

In the 1860's, most of Winnipeg's (then called the Red River Settlement) inhabitants either lived in farmsteads lying along the river banks (patterned after the French-Canadian seigneurial system) or in a village at Point Douglas. When Henry McKenney built a general store at the intersection of the two dirt roads, he was mocked -- at the time, the closest building was Upper Fort Garry, located on the north bank of the Assiniboine, a half-mile south of the crossroads. Other businessmen, however, followed suit with McKenny, and the intersection quickly became busy. The first meeting of the Winnipeg City Council took place in the second floor of a hardware store located at the northwest corner of the intersection in January 1874.

In 1881, the Canadian Pacific Railway arrived in the city, followed by the Grand Trunk Pacific and the National Transcontinental (later to amalgamate into the Canadian National Railways, or CN). The arrival of the railroads sparked an economic boom in Winnipeg, and the area around Portage and Main became the commercial center of the city. As with the oxcart paths, the railroads converged near Portage and Main, and CN built its Union Station just south of the intersection in 1912. The boom, and its demand for land, led to the demolition of Upper Fort Garry in 1882 (only the north gate remains from the original structure). In 1892, streetcar lines were laid through the intersection.

A commodities and agricultural futures exchange (now the Winnipeg Grain Exchange) was founded in 1887, and moved to Portage and Main in 1906. Many of the banks, warehouses and brokerage houses built in the period from 1881 to 1918 still stand, and are now known as the Exchange District (now a National Historic Site). The Bank of Montreal building, with its Roman temple facade, was added to the southeast corner of the crossroads in 1911, where it stands to this day.

After World War I and the opening of the Panama Canal, the railroad boom subsided. In the summer of 1919, some 40,000 workers walked away from their jobs during the Winnipeg General Strike. Several bloody clashes between strikers and policemen (both local constables and troops from the North-West Mounted Police) occured on the streets, including Portage and Main.

The 1920's saw the further development of the area around the intersection, including the construction of the new Hudson's Bay Company store on Portage Ave., and the new Grain Exchange Building, then Canada's largest office building.

The stock market crash of 1929, the Great Depression and World War II would all contribute to a slowing of the development of Winnipeg's downtown on the whole, and Portage and Main was hardly an exception. In 1950, the intersection was covered with water (and, to a lesser extent, human waste) after the Red River spilled its banks in a disastrous flood.

This wasn't to change until 1969, when a 20-year construction binge radically altered the intersection, and with it, Winnipeg's skyline. That year would see the completion of the Richardson Building on the northeast corner. The Richardson Building topped off at 407', and would reign ans the city's tallest building for two decades. In 1978, and underground concourse was constructed, and pedestrian traffic was barred from the intersection. Winnipeg winters are severe, but Winnipeggers have an intimate connection to Portage and Main, so the concourse was seen as a mixed blessing at best. The next year saw the opening of the new Commodity Exchange Tower (also known as the Trizec Building) on the southwest corner. Trizec is slightly smaller then the Richardson Building, but has the advantage of housing Winnipeg Square, an underground shopping mall connected to the concourse. The venerable Bank of Montreal building was joined by a 24-tower office complex in 1983. The final corner to get a facelift was the northwest corner, occupied by the Toronto Dominion Bank. TD leveled their elegant (but small and threadbare) building in favor of a new 413' tower, replete with a postmodern glass facade and front plaza.

Portage and Main still acts as a gathering place for Winnipeggers. Both Bobby Hull and Dale Hawerchuk signed their first contracts with the Winnipeg Jets at ceremonies held at the intersection. Parades held in the city always wind their way through the intersection, usually to their endpoint at The Forks. Despite the barricades, celebrants flooded the intersection to celebrate Canada's ice hockey victory at the 2002 Winter Olympics.